Clonidine therapy enhancement

Abstract

This invention provides methods for intraspinal administration of therapeutically-effective amounts of clonidine for alleviating acute and chronic pain.

We claim: 
     
       1. A method for achieving an analgesic effect in a human, the method comprising intraspinal administration to the human of an increasing and analgesically-effective dose of clonidine over a treatment period whereby administration is unaccompanied by clinically-adverse hemodynamic effects. 
     
     
       2. The method of claim 1, wherein the clinically-adverse hemodynamic effect is hypotension. 
     
     
       3. The method of claim 1, wherein the clinically-adverse effect is bradycardia. 
     
     
       4. The method of claim 1, wherein clonidine is administered intrathecally. 
     
     
       5. The method of claim 1, wherein clonidine is administered epidurally. 
     
     
       6. The method of claim 1 wherein clonidine is administered intrathecally to the cervical spine, the thoracic spine, the lumbar spine or the sacral spine. 
     
     
       7. The method of claim 1, wherein clonidine is administered intrathecally using an implantable, programmable drug administration system or device. 
     
     
       8. The method of claim 1, wherein clonidine is administered over a treatment period of from about 4 to about 12 weeks. 
     
     
       9. The method of claim 1, wherein clonidine is continuously administered. 
     
     
       10. The method of claim 1, wherein clonidine is administered at a dose of from about 4 to about 50 μg/hr during at least a portion of the treatment period. 
     
     
       11. The method of claim 1, wherein clonidine is administered at about 1 to about 4 μg/hr at the beginning of the treatment period. 
     
     
       12. The method of claim 1, wherein clonidine is administered at about 40 to 50 μg/hr at the end of the treatment period. 
     
     
       13. The method of claim 1, wherein the dose of clonidine administered is increased by about 0.2 to about 5 μg/hr. 
     
     
       14. The method of claim 1, wherein the dose of clonidine administered is increased from once to about three times per day. 
     
     
       15. The method of claim 1 wherein the dose of clonidine administered is from about 450 to about 1200 μg/day. 
     
     
       16. The method of claim 1, wherein the dose of clonidine administered is therapeutically-effective in alleviating chronic neuropathic pain in the human. 
     
     
       17. The method of claim 1, wherein the dose of clonidine administered is therapeutically-effective in alleviating chronic neuropathic pain in the human associated with spinal cord injury, plexopathy, diabetic neuropathy, post-herpetic neuralgia, phantom limb pain, stump pain in amputees, peripheral neuropathy, peripheral nerve injury, AIDS neuropathy, reflex sympathetic dystrophy, or primary or metastatic neoplasia. 
     
     
       18. The method of claim 1, wherein said dose of clonidine is administered at a concentration in excess of 500 μg/mL. 
     
     
       19. The method of claim 1, wherein said dose of clonidine is administered at a concentration of about 500 to 4000 μg/mL. 
     
     
       20. The method of claim 1, wherein said dose of clonidine is administered at a concentration of about 1000 to about 2000 μg/mL. 
     
     
       21. A method for achieving an analgesic effect in a human having a heart beat, the method comprising the steps of: monitoring the heart beat in the human; and   administering intraspinally to the human an increasing and analgesically-effective dose of clonidine over a treatment period in a dose responsive to the step of monitoring the heart beat to minimize or eliminate bradycardia.   
     
     
       22. A method for achieving an analgesic effect in a human body, the method comprising the steps of: implanting in the body, a reservoir of clonidine and a delivery system for the clonidine, the delivery system connected to the reservoir; and   administering intraspinally to the human body, from the reservoir and through the delivery system, an increasing and analgesically-effective dose of clonidine over a treatment period.   
     
     
       23. A method for achieving an analgesic effect in a human body, the method comprising the steps of: implanting in the body, a reservoir of clonidine and a delivery system for the clonidine, the delivery system connected to the reservoir; and   administering intraspinally to the human body, from the reservoir and through the delivery system, an increasing and analgesically-effective dose of clonidine over a treatment period,   whereby administration is unaccompanied by adverse hemodynamic or pulmonary effects.   
     
     
       24. A method for achieving an analgesic effect in a human, the method comprising the steps of: monitoring hemodynamic effects in the human; and   administering intraspinally to the human an increasing and analgesically-effective dose of clonidine over a treatment period, said dose responsive to the step of monitoring hemodynamic effects to minimize or eliminate hemodynamic effects,   whereby administration is unaccompanied by adverse hemodynamic effects.   
     
     
       25. The method of claims 21, 22, 23 or 24 wherein the clonidine is administered intrathecally. 
     
     
       26. The method of claims 21, 22, 23 or 24 wherein the clonidine is administered over a treatment period of from about 4 to about 12 weeks. 
     
     
       27. The method of claims 21, 22, 23 or 24 wherein the clonidine is continuously administered. 
     
     
       28. The method of claims 21, 22, 23 or 24 wherein the dose of clonidine administered is therapeutically-effective in alleviating chronic neuropathic pain in the human. 
     
     
       29. The method of claims 21, 22, 23 or 24 wherein said dose of clonidine is administered at a concentration in excess of 500 μg/mL. 
     
     
       30. The method of claims 21, 22, 23 or 24 wherein said dose of clonidine is administered at a concentration of about 500 to 4000 μg/mL. 
     
     
       31. The method of claims 21, 22, 23 or 24 wherein said dose of clonidine is administered at a concentration of about 1000 to about 2000 μg/mL.